Zelnorm | For Irritable Bowel Syndrome Constipation
Zelnorm Withdrawn from USA Market by the FDA 2007
Are there safer alternatives to Zelnorm? Zelnorm is a medication meant for the short-term treatment of Irritable Bowel Syndrome in constipation-predmominant women. Zelnorm is a prescription drug for IBS abdominal pain, bloating, discomfort and constipation.
Zelnorm is not to be prescribed to women with diarrhea-predominant Irritable Bowel Syndrome.
Zelnorm is not to be prescribed to men with Irritable Bowel Syndrome.
Zelnorm can only be prescribed to men for chronic idiopathic constipation.
As Zelnorm only received US FDA approval in July 2002, the medication has not been on the market long enough to determine safety or effectiveness for lifelong use. Zelnorm has not been shown to work in men with Irritable Bowel Syndrome. In 2005 the European Union refused to accept Zelnorm as a medication for Irritable Bowel Syndrome. In 2006 the EU reiterated their rejection of Zelnorm.
- Zelnorm - How well does it work?
- What is Zelnorm?
- Who should NOT take Zelnorm?
- Zelnorm clinical trials
- Controversy over Zelnorm approval
- Zelnorm side effects
- Zelnorm prices
- Zelnorm alternatives
- IBS Constipation Diet Cheat Sheet
What is Zelnorm? ~ Zelnorm (the generic name is tegaserod) is a drug manufactured by Novartis Pharmaceuticals, and available by prescription only, in the US, Canada, Australia, South Africa, and over 30 other countries (where it may be called Zelmac). Zelnorm is classified as a 5-HT4-receptor agonist, which means that it imitates the action of serotonin (a neurotransmitter) in your gut. Ninety-five percent of serotonin in the body is found in the gastrointestinal tract (the balance is found in the brain). In plain English, Zelnorm acts on nerve cells to speed the colon's movement of stools.
The recommended Zelnorm dosage is 6 mg tablets taken twice daily on an empty stomach, shortly before meals. Zelnorm is only meant to be used for 4 to 6 weeks. For patients who respond well to Zelnorm, an additional 4 to 6 week course can be considered. Zelnorm is not meant to be taken only as needed; it is a twice-daily maintenance drug. Zelnorm is meant to increase the movement of stools through the bowels, which relieves the IBS symptom of constipation, but Zelnorm does not cure IBS (nothing does). For those who are helped by Zelnorm, the drug can reduce abdominal pain and discomfort, bloating, and constipation. Once you stop taking Zelnorm your IBS constipation and other symptoms will likely return very shortly. For safe lifelong management and prevention of constipation and bloating due to Irritable Bowel Syndrome, the IBS diet and a soluble fiber supplement such as organic Tummy Fiber Acacia are healthy alternatives. Fennel is a safe herbal tea that can be extremely beneficial for bloating associated with IBS.
Who should NOT take Zelnorm? ~ Zelnorm is not recommended for use by pregnant or breast-feeding women, and it is absolutely not to be used by women with diarrhea. Zelnorm is not established as safe for children, and its use in children is not recommended. The drug should also not be used by women who have a kidney or liver disease; a bowel obstruction (intestinal blockage); symptomatic gallbladder disease; or abdominal adhesions. Zelnorm should not be used by patients who are allergic to any of its active or inactive ingredients, which include lactose (milk sugar). Zelnorm should not be used by men with Irritable Bowel Syndrome. Zelnorm should not be used by men or women with chronic idiopathic constipation if they are over age 65.
Zelnorm clinical trials ~ The FDA based its decision to approve Zelnorm on the results of three randomized, double-blind, placebo-controlled clinical studies each lasting 12 weeks. In these clinical trials, the most common possible side effects of Zelnorm were: abdominal pain; headache; diarrhea; nausea; gas; back pain; indigestion; upper respiratory tract infection; flu-like symptoms; sinusitis; urinary tract infection. A slight increase in abdominal surgeries (particularly gall-bladder removal) among Zelnorm users was noted during one of the trials.
The FDA was expected to approve Zelnorm one whole year before it actually did. This anticipated approval was abruptly halted as a result of concerns about an increase in gallbladder and other abdominal operations among patients testing the drug. European regulators raised similar concerns. Post-approval, the FDA has ordered Novartis to study how patients fare as sales begin, and pledged to closely monitor any reports of side effects.
In March 2006, a panel of European experts rejected Zelnorm for the European market for the second time, after re-examining the evidence following the initial December 2005 rejection of the drug.
The CHMP was concerned that the results of the study would not translate into real benefit to the patient treated to relieve the symptoms of this disorder in standard health care setting. The CHMP was of the opinion that Zelnorm’s benefits are not greater than its risks. Hence, the CHMP recommended that Zelnorm be refused marketing authorisation.
The London-based European Medicines Agency said the committee had reiterated the decision from December not to recommend Zelnorm for the relief of irritable bowel syndrome in women with constipation.
Controversy over Zelnorm approval ~ A consumer advocacy group has attacked the FDA's approval, claiming that officials were ignoring early signals of Zelnorm risks just as the agency earlier downplayed the bowel inflammations and other complaints that eventually derailed the IBS-diarrhea drug Lotronex. The advocacy group Public Citizen (a national non-profit organization that accepts no government or corporate money) contends that the approval of Zelnorm is a serious mistake by the FDA, and that there is no proof Zelnorm relieves constipation better than soluble fiber supplements. Drs. Elizabeth Barbehenn, Ph.D. and Sidney M. Wolfe, M.D. of Public Citizen claim Zelnorm is "a drug that is, at best, minimally effective and that may be causing substantial harm." Public Citizen's letter to the FDA regarding Zelnorm has been made publicly available.
Zelnorm side effects ~ During clinical trials, the following list of adverse events occurred more often in patients on Zelnorm than in patients on the placebo:
Body as a Whole: abdominal pain, chest pain, flushing, facial edema
Cardiovascular: hypertension, hypotension, angina pectoris, syncope, arrythmia
Central Nervous System: anxiety, vertigo
Female Reproductive: ovarian cyst, miscarriage, menorrhagia
Gastrointestinal: cholecystitis, appendicitis, bilirubinemia, gastroenteritis
Metabolic: increased creatine phosphokinase
Musculoskeletal: back pain, cramps
Neoplasms: breast cancer
Psychiatric: attempted suicide, impaired concentration, increased appetite, sleep disorder, sleep disorder, depression, anxiety
Respiratory: asthma
Skin: pruritis, increased sweating
Urinary: renal pain, polyuria
If you experience any side effects while taking Zelnorm, call your doctor. If you experience new or worsening abdominal pain not typical of your IBS, call your doctor.
Zelnorm Prices ~ In the US, Novartis estimates that Zelnorm tablets will sell for somewhere in the range of $3 to $4 each. The drug is expected to generate $1 billion in annual sales for Novartis.
Zelnorm Withdrawn from USA Market by FDA
As of March 30, 2007, the Food and Drug Administration (FDA) has requested that Novartis Pharmaceuticals voluntarily discontinue marketing of Zelnorm (tegaserod) based on the recently identified finding of an increased risk of serious cardiovascular adverse events (heart problems) associated with use of the drug. Novartis has agreed to voluntarily suspend marketing of the drug in the United States.
Zelnorm is a prescription medicine approved in July 2002 for short-term treatment of women with irritable bowel syndrome whose primary symptom is constipation. It was subsequently approved in August 2004 for treatment of chronic constipation for men and women under age 65. Zelnorm is marketed in 55 countries.
FDA is currently advising patients who are using Zelnorm to contact their health care providers to discuss treatment alternatives. Patients who are taking Zelnorm should seek emergency medical care if they experience severe chest pain, shortness of breath, dizziness, sudden onset of weakness or difficulty walking or talking, or other symptoms of a heart attack or stroke.
"This decision reflects the FDA's commitment to continuously monitor approved drugs throughout their marketing life, and take action when we believe the risks exceed the benefits," said Dr. Douglas Throckmorton, Deputy Director for the Center for Drug Evaluation and Research. "Here, a potential risk of very serious harm to patients who have this non-life-threatening condition was recently identified, making this action necessary."
Throughout February and March 2007, Novartis reported to FDA the results of a new analysis of 29 short-term (1 - 3 months) randomized, controlled clinical trials of Zelnorm. FDA has concluded, based on these data that for most patients the benefits of this drug no longer outweigh the risks.
The analysis included more than 11,600 patients treated with Zelnorm and over 7000 patients treated with placebo. The data showed that the risk of serious cardiovascular adverse events (e.g., angina, heart attacks, and strokes) associated with use of Zelnorm is higher than with placebo treatment. Thirteen Zelnorm-treated patients (or 0.1%) had confirmed cardiovascular ischemic events, and only 1 placebo-treated patient (or 0.01%) with an event.
FDA will work with Novartis to allow access to Zelnorm as an investigational drug for patients with no other treatment options where the benefits may outweigh the risks. FDA has also indicated to Novartis the possibility of considering limited re-introduction of Zelnorm at a later date if a population of patients can be identified in which the benefits of the drug outweigh the risks. Any such proposal would be the subject of a public advisory committee meeting before an FDA decision.
If you have Zelnorm in your possession, call 1-888-669-6682 after Monday April 9th, 2007 for information on how to obtain a refund.
FDA Permits the Restricted Use of Zelnorm
As of August 2007, under an investigational new drug protocol program, restricted use of tegaserod maleate has been approved to benefit certain patients who have no other treatment options. Under the protocol, tegaserod may only be used to treat irritable bowel syndrome with constipation and chronic idiopathic constipation in women younger than 55 years who have had no satisfactory response to other available treatments or had satisfactory improvement of symptoms during prior tegaserod therapy.
Key exclusion criteria for tegaserod use include a history or current diagnosis of cardiovascular ischemic disease, symptoms suggestive of cardiovascular ischemic disease, the presence of any cardiovascular risk factors according to National Institutes for Health guidelines, and uncompensated depression or anxiety or suicidal ideation or behavior. Tegaserod will remain off the market for general use.
Novartis Notifies the FDA They Will No Longer Provide Zelnorm Under a Treatment Investigational New Drug Application
As of April 2, 2008, Novartis, the manufacturer of Zelnorm, has notified the FDA that they will no longer provide Zelnorm (tegaserod maleate) under a treatment investigational new drug application (T-IND) protocol to treat irritable bowel syndrome with constipation (IBS-C) and chronic idiopathic constipation (CIC) in women younger than 55.
Novartis has agreed to continue to supply Zelnorm for use in emergency situations. Requests for Zelnorm for this purpose may be made to the FDA which in turn authorizes shipment of the drug by the manufacturer.
An emergency situation is defined as one that is immediately life-threatening or serious enough to qualify for hospitalization. FDA may deny authorization, even in life-threatening situations, if available evidence fails to provide a reasonable basis for concluding that Zelnorm may be effective for the intended use, or if exposure to Zelnorm would pose an unreasonable or a significant additional risk to patients. The following conditions are cause for denial of authorization:
prior history of heart attack or stroke
unstable angina
hypertension
hyperlipidemia
diabetes
age greater than 55 years
smoking
obesity
depression
anxiety
suicidal ideation
Physicians with patients who may qualify for treatment with Zelnorm for emergency use may contact FDA’s Division for Drug Information about the emergency IND process
Alternatives to Zelnorm
For safe and effective non-drug approaches to managing IBS symptoms, check here to learn how the organic soluble fiber Acacia can help relieve constipation without risks or side effects, why fennel can be extremely beneficial for bloating, how peppermint can relieve and prevent abdominal pain, and how gut-directed hypnotherapy addresses the underlying pathology of bowel dysfunctions and relieves all IBS symptoms.
If you feel confident that your constipation and bloating are symptoms of Irritable Bowel Syndrome, information is key. Learn all you need to know about this disorder with The First Year: IBS, an essential guide to successfully managing Irritable Bowel Syndrome.
Earlier FDA Zelnorm Warnings
On April 29, 2005, the Food and Drug Administration (FDA) and Novartis notified healthcare professionals of revisions to the warnings and precautions sections of labeling for tegaserod maleate (Zelnorm). The warning refers to serious consequences of diarrhea (including hypovolemia, hypotension, and syncope) that occurred both during clinical trials and during marketed use, in some cases requiring hospitalization.The warning refers to serious consequences of diarrhea (including hypovolemia, hypotension, and syncope) that occurred both during clinical trials and during marketed use, in some cases requiring hospitalization. Zelnorm is prescribed for the short-term treatment of women with irritable bowel syndrome whose primary bowel symptom is constipation.
According to the FDA, Zelnorm should be discontinued in patients who develop hypotension or syncope. It should not be initiated in patients who frequently experience or are currently experiencing diarrhea. The FDA recommends discontinuation of the drug in patients who develop symptoms of ischemic colitis such as rectal bleeding, bloody diarrhea, or new/worsening abdominal pain. These patients should be evaluated promptly and treatment with Zelnorm should not be resumed if a diagnosis of ischemic colitis is confirmed.
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On April 28, 2004, the Food and Drug Administration (FDA) announced the addition of serious new risk information to the health professional labeling for Zelnorm. The specific revisions include:- a new warning about the serious consequences of diarrhea associated with the medication
- a new precaution about ischemic colitis and other forms of intestinal ischemia (reduced blood flow to the intestines)
- changes to the adverse reactions section describing post-marketing reports
- new information in the "Information for the Patient" leaflet
"The FDA currently has 21 reports of diarrhea so severe that it caused such complications as low blood pressure and fainting. Sixteen patients required hospitalization," said the FDA's Dr. Robert Justice.
The new precaution on ischemic colitis states: "Ischemic colitis, and other forms of intestinal ischemia, have been reported in patients receiving Zelnorm during marketed use of the drug. A causal relationship between Zelnorm use and these events has not been established. Placebo-controlled clinical trials of 7,000 patients for 3-month duration showed no cases of these events, and would suggest the rate of these events is low. Zelnorm should be discontinued immediately in patients who develop symptoms of ischemic colitis, such as rectal bleeding, bloody diarrhea or new or worsening abdominal pain. Patients developing these symptoms should be evaluated promptly and have appropriate diagnostic testing performed. Treatment with Zelnorm should not be resumed in patients who develop findings consistent with ischemic colitis."
"Since Zelnorm went on sale in 2002, the FDA has received 20 reports of ischemic colitis, plus three reports of a similar intestinal problem," Justice said. "Fourteen patients were hospitalized. Four died, although they had numerous other serious medical conditions."
Under the post marketing experience heading in the adverse reactions section, the labeling now states: "Voluntary reports of adverse events occurring with the use of Zelnorm include the following: ischemic colitis, mesenteric ischemia, gangrenous bowel, rectal bleeding, syncope, suspected sphincter of Oddi spasm, bile duct stone, and cholecystitis with elevated transaminases. Because these cases are reported voluntarily from a population of unknown size, estimates of frequency cannot be made. No causal relationship between these events and Zelnorm use has been established. Hypokalemia secondary to diarrhea has also been reported."
The new patient information advises patients who get new or increased stomach pain or blood in their stools to stop taking Zelnorm right away and to immediately contact their doctor to determine if they may have a serious problem. In addition, the new labeling advises patients to stop taking Zelnorm and to call a doctor right away if they experience diarrhea that leads to lightheadedness, dizziness or fainting. In conjunction with today's FDA announcement, the manufacturer of Zelnorm, Novartis Pharmaceuticals Corporation of East Hanover, N.J., has issued a letter to health professionals to highlight the labeling changes.
For safe and effective non-drug approaches to managing IBS symptoms, learn how the organic soluble fiber Tummy Fiber Acacia can help relieve constipation without risks or side effects, why high volatile oil fennel tea can be extremely beneficial for bloating, how peppermint oil capsules can relieve and prevent abdominal pain, and how gut-directed hypnotherapy addresses the underlying pathology of bowel dysfunctions and relieves all IBS symptoms.
If you feel confident that your constipation and bloating are symptoms of Irritable Bowel Syndrome, information is key. Learn all you need to know about this disorder with The First Year: IBS, an essential guide to successfully managing Irritable Bowel Syndrome.
IBS Constipation Diet Cheat Sheet
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 Excerpted from Eating for IBS. |
Zelnorm clinical information supplied by the Novartis Zelnorm Patient Prescribing Information drug insert.
